Thursday, September 15, 2016

The glycogenin is a protein whose main function is to be the initiator molecule of glycogen synthesis (glycogenesis), a process that allows the storage of glucose residues in the form of a polysaccharide. Glucose residues are added to glycogenin through α-1,4 bonds. The first step in the glycogen synthesis is indeed the synthesis of this protein. Each glycogen molecule is linked to a glycogenin by a glycosidic linkage which involves the first glucose residue of the chain and a tyrosine residue of glycogenin. The glycogenin designation stems from the fact that this protein is involved in the genesis of glycogen, by functioning as a primer in the formation of a new glycogen molecule.The glycogenin through its glucosyltransferase activity, binds covalently to itself a glucose molecule (from UDP-glucose - the active form of glucose). Then, the glycogenin forms a compact complex with glycogen synthase, the enzyme responsible for glycogen synthesis. After the addition of up to 7 more glucose residues (from UDP-glucose) mediated again by the activity of glucosyltransferase of glycogenin. Finally, glycogen synthase and branching enzyme enter in action, being glycogenin covalently linked to the unique reducing end of the glycogen molecule.
In humans there are two isoforms of glycogenin which can be expressed as glycogenin-1, having a molecular weight of 37 kD, and encoded by the GYG gene that is expressed mainly in muscle, or as glycogenin-2 having a molecular weight of 66 kDae encoded by GYG2 gene which is expressed mainly in the liver, cardiac muscle and other types of tissues except skeletal muscle

Disability glycogenin-1 (GYG1) - Mutation of the gene GYG1
A glycogenin-1 deficiency was detected in its gene, GYG1, which revealed a nonsense mutation in one allele and a missense mutation in another allele. A missense mutation results from inactivation of the autoglycosilation of glycogenin-1, which is required for the initiation of glycogen synthesis in muscle. The glycogenin-1 autoglycosilation occurs at Tyr195 by the action of glucose-1-O-tyrosine. A missense mutation of this residue results in inactivation of the autoglycosilation. However, it was also demonstrated that missense mutations affecting other residues of glycogenin 1-cause problems on autoglycosilation.
Phenotypic characteristics of skeletal muscle in a patient with this disorder are muscle glycogen depletion, mitochondrial proliferation and marked predominance of slow twitch amd oxidized muscle fibers. Mutations in glycogenin-1 gene GYG1 are also causes of cardiomyopathy and arrhythmia.

Tuesday, September 6, 2016

Enolase is an enzyme, more particularly, an active metalloenzyme. This enzyme belongs to the family of lyases, the hydro-lyases, breaking the carbon-oxygen bonds, and is present in all tissues and organisms involved in glycolysis or fermentation. The optimal pH of this enzyme is 6.5 in humans.Its main function is to intervene in the 9th step of glycolysis (the penultimate step in this metabolic pathway), a step in which occurs the dehydration of 2-phosphoglycerate (2-PG) in phosphoenolpyruvate (PEP), a product that will be used in the next and final step for the production of energy (ATP).
Enolase has three different isoforms: the ENO1 or alpha-enolase (in muscle tissue); ENO2 or gamma-enolase or neuro specific enolase (in neurons); ENO3 or beta-enolase (in skeletal muscle cells). Enolase has a molecular weight of about 100000 Daltons (depending on the isoform). In humans, the α-enolase has two antiparallel subunits, which have two domains that establish hydrophobic interactions. The subunits interact via salt bridges, involving arginine and glutamate.
The specific enolase to neurons is released in a wide variety of diseases, such as multiple sclerosis or stroke, or myocardial infarction.
In several medical experiments, it was employed enolase concentrations in samples in an attempt to diagnose certain conditions and its severity. Several studies demonstrated that different levels of enolase may also be associated with tumor growth or with the occurrence of myocardial infarction or stroke, so it was inferred that the levels of enolase serve as an indicative of the prognostic evaluation of victims of cardiac arrest.
Enolase inhibitors have been utilized in health care for the treatment and prevention various diseases, such as anti-trypanosome drugs and more recently as anticancer agents. Enolase can be inhibited by fluoride ion (F-). The fluoride forms a complex with magnesium and phosphate, which binds to the active center of the enzyme rather than the substrate 2-PG, preventing the conversion of 2-PG into PEP, decreasing the production of PEP and, consequently, ATP.
Intake of fluoride-containing water inhibits the catalytic activity of enolase of bacteria present in oral cavity (highly dependent on glycolysis due to the anaerobic environment), interrupting glycolysis and, thus, bacterial fermentation (decreased acid production), preventing the formation of dental caries.

Sunday, August 28, 2016

Carbohydrates play a variety of functions in nature. Because of this, they are
indispensable elements for living beings. The main functions of carbohydrates
are:

- Metabolic fuel – various
monosaccharides may be used as a source of chemical energy through its
catabolism. Logically, the main carbohydrate used as metabolic fuel is glucose.
However, there are several other monosaccharides that can also be used as
metabolic fuel (more information on this subject here),
such as fructose, mannose or galactose;

- Nucleotide components– this
function is performed by two different pentose, ribose and deoxyribose. Actually,
only one of these carbohydrates is a “pure” monosaccharide (ribose), the other
is a derivative of monosaccharide (deoxyribose). Soon, I will write a post about
this... Both ribose and deoxyribose are pentoses, that means, they are monosaccharides
with 5 carbons. Ribose enters in the composition of ribonucleotides (and
consequently RNA) while deoxyribose takes part of the composition of
deoxyribonucleotides (and hence the DNA);

- Metabolic fuel reserve - some
polysaccharides play the function of metabolic fuel reserve. In this context,
there are two molecules that deserve a highlight: starch and glycogen. Both are
composed of a single type of monosaccharide, glucose. Starch is the reserve polysaccharide
of glucose in plant cells, while glycogen is the reserve polysaccharide in
animal cells;

- Structural function - some
polysaccharides play structural functions, including cellulose and
peptidoglycan. The first is the main component of cell walls of plant cells,
while the latter is the main component of the cell wall of prokaryotes;

- Protection - some polysaccharides
play a protective function, such as chitin, which is the main component of the
exoskeleton of insects;

- Lubrication and hydration - due to
their rich composition in hydrophilic functional groups, carbohydrates have the
ability to interact with a large number of water molecules. Because of this
feature, various polysaccharides form viscous and highly hydrated mixtures.
These polysaccharides are referred to as glycosaminoglycans and are essential
for the skin, joints, etc.

- Recognition and cell adhesion -
there are several molecules involved in cell adhesion and recognition. These
molecules are found on the cell surface and have carbohydrate
components, being called glycoproteins or glycolipids.

Sunday, August 21, 2016

Cytochromes were first described in 1884 by MacMunn as respiratory pigments. Later, in 1920, Keilin rediscovered these respiratory pigments and
gave them the name of Cytochrome, classifying these heme proteins based
on the lowest level of the cytochrome energy absorption position.Cytochrome
c is a small protein with 104 amino acids located in the intermembrane
space of mitochondria of all living beings who do aerobic respiration. Part of its chain is separated by a matrix protease when the polypeptide is
inserted into the inner membrane, being anchored in a proper
orientation.It is a heteroprotein (protein composed of amino acids and other
chemical elements), which besides amino acids, has a heme group
(cofactor)that is bound to the cysteines 14:17.It is a hydrophilic protein, highly soluble in water (solubility ~100g /L).The
percentage of each type of amino acid present in the protein varies,
depending on the species and it is related to their evolutionary proximity.
The
variation in the primary structure in different species, indirectly
reveals their genetic differences since the code for the protein is
written in the genes. This protein plays an important role in cellular respiration as it is an electron carrier between complexes III and IV, displacing them to an oxygen molecule (final acceptor), thereby
converting molecular oxygen to two molecules of water. In
this process, it occurs translocation of protons to the intermembrane space, which help the
formation of a chemiosmotic potential used by the ATP synthase for the
formation of ATP. It
is also responsible for stimulating programmed cell death, or
apoptosis, by activating the intrinsic pathway of the process. This
leads to activation of caspase 9, which in turn activates caspases 3
and 7, and the target cell dies by
apoptosis. Finally, it also promotes the release of calcium stored in the
endoplasmic reticulum, increasing the ion concentration in the cytosol.Regarding the formation of cytochromes, they suffer reversible changes in
the iron oxidation number, changing between +2 and +3 in a cyclical process. There are three main groups of cytochromes, denominated by the letters a, b and c. They
differ in the structure of the prosthetic group (side chain), leading
to different absorption spectra, wherein the cytochrome c absorbs the
shorter wavelengths.

Monday, August 15, 2016

Carbohydrates, also referred to as sugars, are a class of biomolecules
characterized by the presence of many polar groups in its composition. The
building block of the carbohydrates are the monosaccharides, since any
carbohydrate has one, or more than one, monosaccharide. Consequently, they can
be grouped into different classes, namely, monosaccharides, oligosaccharides
and polysaccharides.

When only one or a few monosaccharides are present, usually the carbohydrate
has a sweet taste and is therefore referred to as sugars. In fact, when looking
for a label of a food product, it is common an information like
"Carbohydrates of which sugars". This information may cause some
confusion, because in fact there is some ambiguity in the designation of sugar.
If some people call sugars to carbohydrates, there are those who use this
designation only to carbohydrates that are sweet.
Carbohydrates are the most abundant class of biomolecules in nature, being also
the most abundant class of biomolecules in our food, and should correspond to
45-75% of total energy intake.
Carbohydrates exist in a free form, i.e. without being linked to other types of
molecules. In this case, they are referred to as poly-hydroxyaldehydes or
poly-hydroxyketones, since they present several hydroxyl groups and one
carbonyl group which can be aldehyde or ketone, respectively (if you have any
questions about these functional groups, you can find more information about
them HEREand HERE).

If carbohydrates are combined with other molecules, the resulting molecule is
referred to as a glycoconjugate, being the most well-known glycoconjugates the
glycoproteins and glycolipids.

Thursday, August 11, 2016

Catalase, or hydroperoxidase, is an intracellular enzyme found in most organisms. This protein is found in the peroxisomes, glyoxisomes (plant peroxisome) and in the cytoplasm of prokaryotes. Catalase is an oxidoreductase, since it uses hydrogen peroxide (H2O2)both as an acceptor of electrons and as an electronic donor, decomposing it accordingly to this chemical reaction: 2H2O2 → 2H2O + O2.Although there are various known forms of this enzyme, it is commonly found in the form of a tetramer of 240 kDa, having four polypeptide chains in a quaternary structure. Each polypeptide chain binds a heme group that has an iron ion, which reacts with the hydrogen peroxide, decomposing the molecule. However, there are also some non-heme catalases, that is, instead of havin heme groups, they have one binuclear manganese center.The toxic H2O2 is a product of the metabolism of our cells, produced, for example, during the peroxisomal β-oxidation of fatty acids, which requires a rapid conversion of it into a chemical species that is harmless the organism. Catalase has the highest known turnover number (kcat): the enzymes is able to decompose 40000000 H2O2 molecules per second! Catalase is also important for certain invading microorganisms, which is used as a defense system against some cells of our immune system whose action rely in the production of H2O2 as an antibacterial agent. Finally, this enzyme is associated with delayed aging mechanism connected to oxidative stress.The reaction catalyzed by this enzyme is a dismutation reaction, i.e., the substrate acts as both reductant and oxidant agent. It is known that it occurs in two basic steps: H2O2 + Fe (III)-E → H2O + O = Fe (IV)-E and H2O2 + O = Fe (IV)-E → H2O + Fe (III)-E + O2.

Fe-E represents the iron ion of the heme group, bound to the enzyme. Catalase is also capable of catalyzing the oxidation of other molecules such as formaldehyde, formic acid and certain alcohols. H2O2 + H2R → 2H2O + R, where R is the oxidized form of the molecule that undergoes the reaction. Metal ions (especially copper (II) and iron (II)) are non-competitive inhibitors, and cyanide and curare behave as competitive inhibitors.Catalase is used also used in the textile industry to remove H2O2 from the tissues, and in some contact lens cleaning products, acting as an antibacterial agent. Currently, it has also been used in beauty masks, combining the enzyme with H2O2 to increase cellular oxygenation of the upper layers of the epidermis.The so-called Catalase Test is used in microbiology and consists in the detection of catalase in bacteria, serving essentially to distinguish staphylococci and streptococci. In this test, peroxide is put in contact with a liquid microorganism culture to be tested if it appears bubbles (oxygen); if so, the organism is catalase-positive (has catalase if staphylococci), otherwise, it is designated catalase-negative (streptococci).

Friday, July 29, 2016

In addition to being used as building blocks for protein synthesis, amino acids
play many other important physiological functions. One is undoubtedly the fact
that there are several amino acids that play neurotransmitter functions:

- Glutamate is the main excitatory neurotransmitter in the central nervous
system. It plays central roles in terms of rapid nerve transmission (i.e. rapid
response to a stimulus), cognition, memory, movement and sensation. It is
recognized by two classes of receptors: ionotropic receptors, which are
receptors that when activated allow ion flow across the membrane; and
metabotropic receptors, which when activated stimulate the production of
secondary messengers.

- Aspartate, it is also an excitatory neurotransmitter of the central nervous
system. Due to biochemical similarities between glutamate and aspartate (more on this subject here),
the actuation mechanism and effects are identical between them (although
glutamate is, from a quantitative point of view, more important than
aspartate).

- Glycine is the simplest amino acid, and has inhibitory functions in the
central nervous system, with particular emphasis on the spinal cord, brain stem
and in the retina. In addition to its role as a neurotransmitter, it also plays
immunomodulatory functions, anti-inflammatory and cytoprotection (cell
protection). The activation of its receptors allows influx of chloride ion.